HPV Testing and Monitoring of Women After Treatment of CIN 3: Review of the Literature and Meta-analysis

Abstract

According to the current guidelines in most western countries, women treated for cervical intraepithelial neoplasia grade 3 (CIN 3) are followed for at least 2 years after treatment by cytology.High-risk human papillomavirus (hrHPV) infections are necessary for the development and maintenance of CIN 3. HrHPV testing could be used to improve monitoring of women treated for CIN 3. This has prompted numerous studies for the implementation of hrHPV testing in monitoring of women treated for CIN 3. Included in this review are 20 studies, published between 1996 and 2003, comparing hrHPV testing with either resection margins or cervical cytology to predict recurrent/residual disease, and 11 of them could be used in a meta-analysis. In the meta-analysis of the 11 studies, the negative predictive value (NPV) for recurrent/residual disease of hrHPV testing was 98% (95% CI 97-99%), that of resection margins 91% (95% CI 87-94%), and that of cervical cytology 93% (95% CI 90-95%). When hrHPV testing was performed in conjunction with cytology, the sensitivity was 96% (95% CI 89-99%), specificity was 81% (95% CI 77-84%), the associated positive predictive value (PPV) was 46% (95% CI 38-54%), and the NPV was 99% (95% CI 98-100%). Combined hrHPV and cytology testing yielded the best test characteristics. We propose to include hrHPV testing in conjunction with cytology for monitoring women treated for CIN 3. Some follow-up visits for women testing negative for both hrHPV and cytology can be skipped. In western countries, this could mean that for women double negative at 6 months, retesting at 12 months should be skipped while keeping the 24-month follow-up visit.

The Value of HPV-HR DNA Testing During the Follow-Up After Treatment of CIN3/AIS

“…2) and almost 70% of patients had both tests negative, which corresponds to results of other studies (14). Given the high sensitivity and concordance in our results we conclude that in our setting (with poorer resources and high quality cytology) it is not cost-effective to perform both tests to all women after conization.…”

“…Many studies have shown that combined testing has the highest sensitivity in detecting a residual/recurrent disease [14]. According to our results both tests show a very good performance in detecting a residual/recurrent disease so depending on the socio-economic aspect both can be used as a primary follow-up tool after conization.…”

Routine follow-up intervals in patients with high-grade squamous intraepithelial lesions (HSIL) and free excision margins can safely be increased in the first two years after Large Loop Excision of the Transformation Zone (LLETZ)

“…A meta-analysis of Zielinski et al showed that the status of excision margins, posttreatment cytology, post-treatment hr-HPV or combinations had a negative predictive value of 91-99%, the positive predictive values of these parameters were 25-51% [17]. Based on this study they proposed to follow-up patients with negative cytology in combination with negative hr-HPV DNA testing less intensively.…”

Breakthroughs and Issues in HPV Genital Infections in relation to Cervical Cancer

“…HPV testing picks up residual disease quicker with higher sensitivity and similar specificity to cytology. Zielinski has proposed combined cytology and HPV testing at 6 and 24 months after treatment and referral back to 5 years cytology screening if all tests are negative 29 .…”